High-dose tranexamic acid reduces blood loss in postpartum haemorrhage

Ducloy-Bouthors Anne-Sophie, Jude Brigitte, Alain Duhamel, Broisin Françoise, Huissoud Cyril, Keita-Meyer Hawa, Mandelbrot Laurent, Tillouche Nadia, Fontaine Sylvie, Le, Depret-Mosser Sandrine, Vallet Benoit, The, Susen Sophie

Description

Our purpose in conducting this study was to determine whether administration of high-dose tranexamic acid (TA) at the time of diagnosis of postpartum haemorrhage (PPH) could reduce blood loss. Methods This was a randomised, controlled, multicentred, open-label trial. Women with PPH >800 mL following vaginal delivery were randomly assigned to receive TA (loading dose 4 g over 1 hour, then infusion of 1 g/hour over 6 hours) or not. In both groups, packed red blood cells (PRBCs) and colloids could be used according to French guidelines. The use of additional procoagulant treatments was permitted only in cases involving intractable bleeding. The primary objective was to assess the efficacy of TA in the reduction of blood loss in women with PPH, and the secondary objectives were the effect of TA on PPH duration, anaemia, transfusion and the need for invasive procedures. Results A total of 144 women fully completed the protocol (72 in each group). Blood loss between enrolment and 6 hours later was significantly lower in the TA group than in the control group (median, 173 mL; first to third quartiles, 59 to 377) than in controls (221 mL; first to third quartiles 105 to 564) ( P = 0.041). In the TA group, bleeding duration was shorter and progression to severe PPH and PRBC transfusion was less frequent than in controls ( P < 0.03). Invasive procedures were performed in four women in the TA group and in seven controls ( P = NS). PPH stopped after only uterotonics and PRBC transfusion in 93% of women in the TA group versus 79% of controls ( P = 0.016). Mild, transient adverse manifestations occurred more often in the TA group than in the control group ( P = 0.03). Conclusions This study is the first to demonstrate that high-dose TA can reduce blood loss and maternal morbidity in women with PPH. Although the study was not adequately powered to address safety issues, the observed side effects were mild and transient. A larger international study is needed to investigate whether TA can decrease the need for invasive procedures and reduce maternal morbidity in women with PPH. Trial registration Controlled Trials ISRCTN09968140 .

Informations

• Publié par: biomed
• Publié le: 01 janvier 2011
• Nombre de lectures: 23
• Langue: English

Extrait

DucloyBouthorset al.Critical Care2011,15:R117 http://ccforum.com/content/15/2/R117

R E S E A R C HOpen Access Highdose tranexamic acid reduces blood loss in postpartum haemorrhage 1* 2,34,5 67 AnneSophie DucloyBouthors, Brigitte Jude, Alain Duhamel, Françoise Broisin , Cyril Huissoud , 8,9 9,1011 1112 Hawa KeitaMeyer, Laurent Mandelbrot, Nadia Tillouche, Sylvie Fontaine, Françoise Le Goueff, 13 1,1415 2,3 Sandrine DepretMosser, Benoit Vallet, for The EXADELI Study Groupand Sophie Susen

Abstract Introduction:Our purpose in conducting this study was to determine whether administration of highdose tranexamic acid (TA) at the time of diagnosis of postpartum haemorrhage (PPH) could reduce blood loss. Methods:This was a randomised, controlled, multicentred, openlabel trial. Women with PPH >800 mL following vaginal delivery were randomly assigned to receive TA (loading dose 4 g over 1 hour, then infusion of 1 g/hour over 6 hours) or not. In both groups, packed red blood cells (PRBCs) and colloids could be used according to French guidelines. The use of additional procoagulant treatments was permitted only in cases involving intractable bleeding. The primary objective was to assess the efficacy of TA in the reduction of blood loss in women with PPH, and the secondary objectives were the effect of TA on PPH duration, anaemia, transfusion and the need for invasive procedures. Results:A total of 144 women fully completed the protocol (72 in each group). Blood loss between enrolment and 6 hours later was significantly lower in the TA group than in the control group (median, 173 mL; first to third quartiles, 59 to 377) than in controls (221 mL; first to third quartiles 105 to 564) (P= 0.041). In the TA group, bleeding duration was shorter and progression to severe PPH and PRBC transfusion was less frequent than in controls (P< 0.03). Invasive procedures were performed in four women in the TA group and in seven controls (P= NS). PPH stopped after only uterotonics and PRBC transfusion in 93% of women in the TA group versus 79% of controls (P= 0.016). Mild, transient adverse manifestations occurred more often in the TA group than in the control group (P= 0.03). Conclusions:This study is the first to demonstrate that highdose TA can reduce blood loss and maternal morbidity in women with PPH. Although the study was not adequately powered to address safety issues, the observed side effects were mild and transient. A larger international study is needed to investigate whether TA can decrease the need for invasive procedures and reduce maternal morbidity in women with PPH. Trial registration:Controlled Trials ISRCTN09968140.

Introduction Postpartum haemorrhage (PPH) remains a leading cause of early maternal death, accounting for about 300,000 deaths worldwide every year, and of morbidity related to anaemia, blood transfusion and haemorrhagerelated ischaemic complications [1,2]. PPH is poorly predictable, but its direct causes are mainly uterine atony, trauma to the genital tract and retained placenta [35]. Accordingly, detailed guidelines have been issued for optimal use of

* Correspondence: annesophie.ducloy@chrulille.fr 1 Pole d’AnesthésieRéanimation, CHU Lille, 2 avenue Oscar Lambret, Lille F 59037, France Full list of author information is available at the end of the article

obstetric interventions and uterotonic drugs [6]. In con trast, haemostatic abnormalities in this setting have long been considered consequences of uncontrolled bleeding, not deserving of early specific treatment. Thus, haemo static drugs are not routinely used as a firstline interven tion in PPH [6,7]. This concept was recently challenged by the demon stration of a relationship between fibrinogen decrease and outcome [8]. At the same time, it was recognized that extensive tissue injury can shift the haemostatic equilibrium toward increased fibrinolysis, contributing to coagulopathy and bleeding [9]. Antifibrinolytic agents, mainly tranexamic acid (TA) and aprotinin, have been

© 2011 DucloyBouthors et al.; licensee BioMed Central Ltd This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited